This is a broad program of research encompassing a range of problem areas and involving a diversity of experimental approaches. It is therefore important that this progress report be organized according to the conceptual framework of the program, which is described in the following outline. Progress within the various segments of the program is summarized in the succeeding project summaries and in more detail in the accompanying publications. Program Area I: Segments Utilizing Chemical Models: A. Nitrosamines and Nitrosation Products: B. Reactions of Peroxidizing Lipids with Proteins and Amino Acids. Program Area II: Segments Utilizing Cell Culture Models: A. Human and other Cell Cultures; B. Bacterial Systems for Investigating DNA Damage and Repair. Program Area III: Segments Utilizing Animal Models; A. Biochemical Toxicology of Perfused Organs and Isolated Hepatocytes; B. Interactions Among Environmental Agents. Program Area IV: Tissue Responses and Subcellular Interactions: A. Carcinogen Effects on Nuclear Function and Other Biochemical Processes; B. Carcinogen-Induced Modifications of Cellular Macromolecules.